The long-term objective of the proposed research is to understand the histogenesis as well as biological behavior of pancreatic carcinoma and elucidate the mechanisms regulating gene expression in malignant pancreatic acinar cell. The proposed research will delineate the extent of structural, functional, and enzymatic differentiation of a transplantable pancreatic acinar carcinoma of rat, established for the first time in our laboratory. Emphasis of the proposed studies is laid on the cytodifferentiation, analysis of secretory (zymogen) protein composition, and of secretory process; all of which should provide basic information regarding the extent of retention of enzymic and functional differentiation in this epithelial malignancy. The presence of morphologically-discernible secretory granules in some neoplastic cells among heterogeneous tumor-cell population and evidence of elaboration of certain specific exocrine pancreatic enzymes by the tumor, will greatly facilitate investigations aimed at elucidating the mechanisms of cytodifferentiation as well as in identifying factors which may modulate such differentiation of neoplastic exocrine epithelium. The proposal also includes studies on the conversion of pancreatic acinar carcinoma into an ascites form and on the development of carcinoma cell liner in culture which retain differentiated structure and function. The techniques involved in the present investigation would be tumor transplantation, immunocytochemistry, light and electron microscopic autoradiography, two-dimensional gel electrophoresis, subcellular fractionation and tissue culture. The proposed studies should further our knowledge of the biological behavior of pancreatic carcinoma. The information obtained should be useful for future studies aimed at elucidating the regulatory process influencing tumor progression.